Due to the limited stability of lithium alkyl compounds in polar solvents at ‘high’ temperatures, reactions with high kinetic barriers are often not feasible. One of such examples is the deprotonation of tertiary amines, which traditionally can only be achieved via complex reaction pathways involving intermediate stages that are sometimes toxic.
In our work, we showed that this reaction is easily accessible at high temperatures and under microwave irradiation in the absence of polar additives. The substrate amine itself acts as a ligand for the lithium alkyl compound and deaggregates it, as evidenced by a solid-state structure obtained. Quantum chemical calculations and in situ FTIR spectroscopy showed that deprotonation is possible at high temperatures. Subsequent optimisation using Design of Experiments confirmed that the closed microwave setup is essential for a successful reaction. The absence of polar additives also promotes the storage stability of the newly formed lithium alkyl compound and allows the subsequent addition of polar additives in desired stoichiometries for synthetic applications. This example of the application of microwave radiation with high and precise energy input has opened up a new approachfor the synthesis of kinetically hindered lithium organyls, which does not require the use of (polar) solvents or complex, toxic reaction pathways.
A. Schmidt§, R. Scheel§, A. Ost, L. Brieger, C. Strohmann* Chem. Eur. J. 2025, e02149.